Cyanogen Bromide → 5-(5-amino-[1,3,4]oxadiazol-2-yl)-4-(4-bromo-2-fluorophenylamino)-3-fluoro-1-methyl-1H-pyridin-2-one

HRID 1366064Notes

Reaction equation

HRID 1366064 reaction equation
[N:1]#[C:2]Br.[Br:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[C:13]([C:21]([NH:23][NH2:24])=[O:22])=[CH:14][N:15]([CH3:20])[C:16](=[O:19])[C:17]=2[F:18])=[C:7]([F:25])[CH:6]=1.C([O-])(O)=O.[Na+]>O1CCOCC1.O>[NH2:1][C:2]1[O:22][C:21]([C:13]2[C:12]([NH:11][C:8]3[CH:9]=[CH:10][C:5]([Br:4])=[CH:6][C:7]=3[F:25])=[C:17]([F:18])[C:16](=[O:19])[N:15]([CH3:20])[CH:14]=2)=[N:23][N:24]=1

Participants

6

Reactant 3

HCID 10476Cyanogen Bromide2×HCID 516892Sodium BicarbonateHCID 666737984-(4-Bromo-2-fluorophenylamino)-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid hydrazide

Product 1

HCID 111654245-(5-amino-[1,3,4]oxadiazol-2-yl)-4-(4-bromo-2-fluorophenylamino)-3-fluoro-1-methyl-1H-pyridin-2-oneYield 89.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Cyanogen bromide (36 mg, 0.31 mmol) was added to a suspension of 4-(4-bromo-2-fluorophenylamino)-5-fluoro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid hydrazide (63 mg, 0.169 mmol) in dioxane (2 mL) followed by an aqueous NaHCO3 (2 mL of a 0.09 M solution) solution. After 17 hours, additional cyanogen bromide (14 mg) was added. After 19 hours, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated under reduced pressure. Crystallization (MeOH:THF) followed by trituration (Et2O:MeOH 5:1) gave clean desired product as a white solid (60 mg, 89%). MS APCI (+) m/z 398, 400 (M+, Br pattern) detected; 1H NMR (400 mHz, CD3OD) δ 8.06 (s, 1H), 7.37 (d, 1H), 7.31 (d, 1H), 7.10 (td, 1H), 3.64 (s, 3H).

Workup

  1. waitAfter 19 hours
  2. extractionextracted with ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customCrystallization (MeOH:THF)

Sources & evidence

ORD record
ord-9a02b56a193c493db47fb2315848c23b
Source dataset
uspto-grants-2011_02
Patent number
US07893065B2

Reaction notes

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